BACKGROUND: Eosinophils play a key role in allergic inflammation and parasitic infections. The synthetic peptide, Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), has been previously shown to activate eosinophils and thus to enhance respiratory burst through the formyl peptide receptors. OBJECTIVE: This study was undertaken to determine the intracellular signaling pathway involved in WKYMVm-stimulated superoxide production by human eosinophils. METHODS: Purified eosinophils from peripheral blood were stimulated with various concentrations (10(-3) to 10 microM) of WKYMVm and the involvement of PI3-kinase and MAP kinases in WKYMVm-triggered superoxide production was investigated using pharmacological inhibitors. RESULTS: WKYMVm-induced superoxide production by eosinophils was strongly inhibited by pretreatment with the PI3-kinase inhibitor LY294002. In addition, pretreatment with the ERK1/2 kinase inhibitor PD98059 resulted in marked inhibition of superoxide production induced by WKYMVm. Indeed, WKYMVm strongly induced phosphorylation of ERK1/2. The ERK1/2 activation by the peptide was transient and peaked after 2 min of stimulation. Furthermore, ERK1/2 activation by WKYMVm was completely inhibited by pretreatment with the PI3-kinase inhibitor LY294002, but not by the PKC inhibitor Ro-31-8220. CONCLUSION: These results suggest that WKYMVm stimulates human eosinophils to induce superoxide production via a PI3-kinase-mediated ERK1/2 pathway. Copyright 2005 S. Karger AG, Basel.
BACKGROUND: Eosinophils play a key role in allergic inflammation and parasitic infections. The synthetic peptide, Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), has been previously shown to activate eosinophils and thus to enhance respiratory burst through the formyl peptide receptors. OBJECTIVE: This study was undertaken to determine the intracellular signaling pathway involved in WKYMVm-stimulated superoxide production by human eosinophils. METHODS: Purified eosinophils from peripheral blood were stimulated with various concentrations (10(-3) to 10 microM) of WKYMVm and the involvement of PI3-kinase and MAP kinases in WKYMVm-triggered superoxide production was investigated using pharmacological inhibitors. RESULTS: WKYMVm-induced superoxide production by eosinophils was strongly inhibited by pretreatment with the PI3-kinase inhibitor LY294002. In addition, pretreatment with the ERK1/2 kinase inhibitor PD98059 resulted in marked inhibition of superoxide production induced by WKYMVm. Indeed, WKYMVm strongly induced phosphorylation of ERK1/2. The ERK1/2 activation by the peptide was transient and peaked after 2 min of stimulation. Furthermore, ERK1/2 activation by WKYMVm was completely inhibited by pretreatment with the PI3-kinase inhibitor LY294002, but not by the PKC inhibitor Ro-31-8220. CONCLUSION: These results suggest that WKYMVm stimulates human eosinophils to induce superoxide production via a PI3-kinase-mediated ERK1/2 pathway. Copyright 2005 S. Karger AG, Basel.
Authors: Mary Ellen Bates; Julie B Sedgwick; Yiming Zhu; Lin Ying Liu; Rose G Heuser; Nizar N Jarjour; Hirohito Kita; Paul J Bertics Journal: J Immunol Date: 2010-05-21 Impact factor: 5.422
Authors: Ma Paz Zafra; Jose A Cañas; Carla Mazzeo; Cristina Gámez; Veronica Sanz; Mar Fernández-Nieto; Santiago Quirce; Pilar Barranco; Javier Ruiz-Hornillos; Joaquín Sastre; Victoria del Pozo Journal: Int J Mol Sci Date: 2015-03-10 Impact factor: 5.923